Intense Chemo Bests Standard in Breast Cancer

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This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

After a decade of follow-up, a highly concentrated chemotherapy regimen of epirubicin, cyclophosphamide, and paclitaxel performed better than conventional treatment with the same drugs in women with high-risk breast cancer.

Note that toxicity was "manageable" and the researchers saw no long-term adverse effects or therapy-related mortality.

SAN ANTONIO – After a decade of follow-up, a highly concentrated chemotherapy regimen for women with high-risk breast cancer outperformed conventional treatment with the same drugs, a researcher said.

In a long-running, randomized trial, an intense dose-dense regimen of three drugs markedly improved both disease-free survival (P=0.0001) and overall survival (P=0.0007), according to Volker Moebus, MD, of Goethe University Frankfurt in Frankfurt, Germany.

Toxicity was "manageable" and the researchers saw no long-term adverse effects or therapy-related mortality, Moebus reported at the San Antonio Breast Cancer Symposium here.

The trial, which started in 1998, involved 1,284 women who had at least four lymph nodes positive for breast cancer, Moebus noted, and were regarded as being at high risk for progression and death. They were randomly assigned to a form of chemotherapy standard at the time or to an experimental regimen.

In either case, patients were given epirubicin (Ellence), cyclophosphamide (Cytoxan), and paclitaxel (Taxol).

In the standard regimen, patients were given four 3-week cycles of epirubicin and cyclophosphamide at doses of 90 and 600 mg/m2, respectively. That was followed by four 3-week cycles of paclitaxel at 175 mg/m2.

In contrast, the experimental regimen involved three 2-week cycles with increased doses of each drug, beginning with epirubicin at a dose of 150 mg/m2, followed by paclitaxel at 225 mg/m2, and then by cyclophosphamide at 2,500 mg/m2.

After a median of 122 months of follow-up, Moebus reported that 56% of women in the experimental arm had relapsed, compared with 47% of those in the standard arm, for a hazard ratio for recurrence of 0.74 (95% CI 0.63 to 0.87).

Also, 69% of women in the experimental arm were still alive compared with 59% of those getting standard therapy, for an HR for death of 0.72 (95% CI 0.60 to 0.87).

In a subrandomization among patients in the experimental arm, the researchers also tested the safety of epoetin alfa (Procrit), used prophylactically to reduce the need for red blood cell transfusions.

The use of the substance increased the risk of thrombosis, Moebus reported, but had no effect on risk of relapse or mortality.

In the U.S., the study is unlikely to have much effect on practice, commented Michaela Higgins, MD, of Massachusetts General Hospital in Boston, who was not part of the study.

"It's excellent data, and this is a highly effective regimen," Higgins told MedPage Today. "The question is what cost does it come at, and do we have regimens that are equally effective but less toxic?"

For U.S. physicians, she said, the change in practice came after a 2003 report that described a dose-dense regimen of doxorubicin (Adriamycin) and cyclophosphamide, followed by paclitaxel.

Results of that trial were similar to those reported by Moebus with what looks like lower toxicity, although Higgins cautioned that the two regimens have not been compared head to head.

Higgins noted that the German trial increased the dose of all the drugs, including cyclophosphamide, and it's not clear what led to the improved efficacy and what contributed to the increased toxicity.

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